Increased peroxisomal fatty acid β-oxidation and enhanced expression of peroxisome proliferator-activated receptor-α in diabetic rat liver
Increased peroxisomal fatty acid β-oxidation and enhanced expression of peroxisome proliferator-activated receptor-α in diabetic rat liver
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DOI：
10.1023/a:1006930513476
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发表时间：
1999-04-01
影响因子：
4.3
通讯作者：
Singh, I
中科院分区：
文献类型：
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作者：
Asayama, K;Sandhir, R;Singh, I
为探讨糖尿病大鼠肝脏过氧化酶体中脂肪酸β-氧化增加是否是由常见的过氧酶体增殖机制介导的，我们用同位素方法测定了棕榈酰辅酶A连接酶(PAL)和木质油酰辅酶A连接酶(LICA)催化的长链(LC)和超长链(VLC)脂肪酸的激活以及LC(棕榈酸)和VLC(甘油酸)脂肪酸的氧化。用免疫印迹法检测乙酰辅酶A氧化酶(ACO)，用Northern印迹法检测PPAR-α、ACO和PAL的表达。糖尿病大鼠肝脏过氧化物体和线粒体的PAL活性分别增加2.6倍和2.1倍。糖尿病过氧化物酶体中木脂酰辅酶A连接酶活性增加了2.6倍。在糖尿病过氧化体和线粒体中，棕榈酸的氧化分别增加了2.5倍和2.7倍，而甘油酸氧化在过氧化体中增加了2.0倍。糖尿病组免疫反应性ACO蛋白增加2倍。糖尿病组PPAR-α、ACO和PAL的mRNA水平分别增加2.9倍、2.8倍和1.6倍。这些结果表明，糖尿病状态下肝脏脂肪酸供应的增加刺激了PPAR-α及其负责脂肪酸代谢的靶基因的表达。
To determine whether the increased fatty acid beta-oxidation in the peroxisomes of diabetic rat liver is mediated by a common peroxisome proliferation mechanism, we measured the activation of long-chain (LC) and very long chain (VLC) fatty acids catalyzed by palmitoyl CoA ligase (PAL) and lignoceryl CoA ligase and oxidation of LC (palmitic acid) and VLC (lignoceric acid) fatty acids by isotopic methods. Immunoblot analysis of acyl-CoA oxidase (ACO), and Northern blot analysis of peroxisome proliferator-activated receptor (PPAR-alpha), ACO, and PAL were also performed. The PAL activity increased in peroxisomes and mitochondria from the liver of diabetic rats by 2.6-fold and 2.1-fold, respectively. The lignoceroyl-CoA ligase activity increased by 2.6-fold in diabetic peroxisomes. Palmitic acid oxidation increased in the diabetic peroxisomes and mitochondria by 2.5-fold and 2.7-fold, respectively, while lignoceric acid oxidation increased by 2.0-fold in the peroxisomes. Immunoreactive ACO protein increased by 2-fold in the diabetic group. The mRNA levels for PPAR-alpha, ACO and PAL increased 2.9-, 2.8- and 1.6-fold, respectively, in the diabetic group. These results suggest that the increased supply of fatty acids to liver in diabetic state stimulates the expression of PPAR-alpha and its target genes responsible for the metabolism of fatty acids.